Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000413639 | SCV000491352 | likely pathogenic | not provided | 2015-12-07 | criteria provided, single submitter | clinical testing | The Q1825X variant in the COL5A1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is predicted to cause loss of normal protein function through protein truncation. The Q1825X variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The Q1825X variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded. |
Labcorp Genetics |
RCV001069019 | SCV001234162 | uncertain significance | Ehlers-Danlos syndrome, classic type | 2019-12-16 | criteria provided, single submitter | clinical testing | This sequence change results in a premature translational stop signal in the COL5A1 gene (p.Gln1825*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 14 amino acids of the COL5A1 protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with COL5A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 372825). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant disrupts a region of the protein in which other variant(s) (p.Cys1835Ser) have been observed in individuals with COL5A1-related conditions (PMID: 19370768, Invitae). This suggests that this may be a clinically significant region of the COL5A1 protein. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |